Microglia and Macrophage Responses in Cerebral Ischemia

  • Guido Stoll
  • Sebastian Jander
  • Michael Schroeter


Focal impairment, or cessation of blood flow to the brain, restricts the delivery of substrates, most importantly oxygen and glucose, and thereby impairs maintenance of ionic gradients. This is followed by depolarization of neurons and glia that release excitatory amino acids (glutamate) into the extracellular space and accumulate Ca2+ (reviewed in Dirnagl et al. (1999)). Ca2+ is a universal second messenger leading to production of proteolytic enzymes and free-radical species, and activation of glutamate receptors. In the center of the ischemic territory, where the flow reduction is most severe, these processes induce rapid cell death. A significant proportion of neurons, however, dies by an internal program of self-destruction, designated apoptosis or programmed cell death (Bredesen (1995)). Apoptotic neurons are intermingled with necrotic neurons in the core of infarctions. In the boundary zone, apoptotic cell death is ongoing during the first week after focal ischemia (Li et al. (1995); Braun et al. (1996); Isenmann et al. (1998)). Accordingly, several studies using modem imaging techniques provided evidence for infarct growth during the first few days after cerebral ischemia (Marchal et al. (1996); Beaulieu et al. (1999)). In experimental animals, mediators of the immune system appear to play an essential role in this secondary infarct growth. Mice lacking interferon regulatory factor (IRF), a nuclear transcription factor, developed similar infarct volumes at 24 hours, but significant differences in favor of the knock-out animals became evident at day 3 (Iadecola et al. (1999)).


Cerebral Ischemia Middle Cerebral Artery Occlusion Microglial Activation Interferon Regulatory Factor Focal Cerebral Ischemia 


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© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Guido Stoll
  • Sebastian Jander
  • Michael Schroeter

There are no affiliations available

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